New START Data Fill in When to Start ART, Now the Question is How

New data from a trial looking at the individual health benefits of starting those living with HIV on antiretroviral therapy (ART) at CD4 cell counts above 350 were released today. The data, from a trial known as START, are further evidence in support of the expansion of ART access worldwide. The data from START should also start the clock on even more substantial engagement with the types of ART programs that are most likely to help people make informed choices to begin and remain on life-saving treatment.

It’s now been nearly four years since the release of trial data showing that people living with HIV who started ART at CD4 cell counts between 350 and 500 were significantly less likely to transmit HIV to their sexual partners, compared with people who started according to national guidelines. That trial—known as HPTN 052—may be the single most important factor behind today’s push to use ART to end the epidemic.

In case you’ve been pre-occupied with other parts of the AIDS response like, for example, the war on drug users in Russia or the imperiled VMMC programs in Africa, see UNAIDS’ 90-90-90 campaign for the frontline example of the ART-to-end-AIDS message. AVAC and other allies have been working with UNAIDS, PEPFAR and governments to try to ensure that this message is accurately conveyed and understood as encompassing prevention beyond ART—including saturation-level coverage of VMMC, targeted PrEP, harm reduction and male and female condoms. For more on this work—and why prevention is “on the line” see our most recent Report.

In the wake of early data from HPTN 052, people living with HIV and their allies were quick to point out that the strongest evidence this trial provided was about the prevention benefit of starting ART “early” (i.e., before national guidelines). HPTN 052 did find that earlier initiation had clinical benefits for the individual, including delaying the time to AIDS events, death and tuberculosis. But for many advocates and activists, these data were not definitive and that a real answer would have to come from the START trial, which was a randomized investigation of exactly this question: does immediate initiation of ART improve individual health for people living with HIV?

Today the answer came in, early, and with resounding clarity: Yes.

The START trial, which enrolled 4,685 people at 215 sites in 35 countries (twenty-seven percent of the participants are women, and approximately half are gay men) looked at rates of AIDS, and serious AIDS-defining illness or death in people with CD4 cell counts above 500 who started ART on enrollment in START, versus those participants who also had CD4 cell counts above 500 and delayed treatment until the initiation criteria dictated by the clinical guidelines in their countries.

At a scheduled interim review of the data, the trial’s Data and Safety Monitoring Board (DSMB) found compelling evidence that the benefits of starting antiretroviral treatment immediately at CD4 cell counts above 500 cells/mm3 outweigh the risks. This conclusion was based on the fact that, over an average follow-up period of three years, the risk of AIDS, other serious illnesses or death was reduced by 53 percent among those in the “early” treatment group versus those who started treatment according to national guidelines.

START effectively validates the direction that the WHO’s Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection had begun to take—initiation regardless of CD4 cell count in many populations, including pregnant women, children under the age of five, and people in serodiscordant couples. And it may settle some concerns about whether earlier initiation was good for the person living with HIV—or just for his or her sexual partners and/or potential children.

But it’s critical to recognize that figuring out when to start is only part of the puzzle. The question of how to start is equally critical and isn’t going to be settled by any randomized trial. The how concerns the environment in which individuals are offered treatment, the services that are part of that offer—peer support, community-based refills, non-biased provider care, among others—and the ways that the decision to start is framed. Even with clinical and public health benefits, ART may not be for everyone as soon as they are diagnosed. Issues with disclosure exist everywhere and are compounded in places where laws criminalizing HIV are on the books.

At a time when funding for civil society organizations is dropping everywhere—and when some PEPFAR country programs are placing funding for community engagement as “near- or non-core” (pieces of USG jargon that set priority for PEPFAR funding) —and when UNAIDS has yet to step forward with staunch, straightforward condemnation of rights-violating legislation and hate speech by politicians, this “How?” question is far from resolved.

That’s why START has to be welcomed for what it is—a clear answer to a critical question. And also understood for what it is not—an answer to the urgent challenge of how best to truly seek to end the epidemic with comprehensive prevention programs that include, but are not restricted to, delivering ART so that everyone who wants it can start it, stay on it, achieve virologic suppression and, more importantly, a life lived with health, dignity and joy.

Selected Guide to Pipeline of Antibodies, Long-Acting ARVs and Vaccines

This graphic provides a quick primer on passive immunization with HIV-specific antibodies, long-acting antiretroviral injectables, and preventive vaccines, including a new, informative table reviewing the pipelines in research and development for all three research avenues.

Burning the Candle at Both Ends: An Advocacy Forum Discussion on “Injectable Prevention”

Ntando Yola has worked for eight years in HIV prevention research at the Desmond Tutu HIV Foundation (DTHF) in Cape Town. In his role as a Community Engagement Coordinator he has worked closely with various national and international HIV prevention Networks. His work has involved working with various community stakeholders, developing and implementing community education programmes, forming partnerships with health service providers and other community based organizations as key stakeholders HIV prevention research. He was also a 2013 AVAC Fellow.

At the 2015 AVAC Partners’ Forum, there was a lot of interest in advocates and activists about the important role scientific research has to play in addressing HIV. How important was it? So important that at a roundtable discussion that started after the day was scheduled to end, a small but dedicated group of participants spent over an hour talking about the current pipeline of “injectable prevention” which includes long acting injectable PrEP (I am currently working at DTHF in Cape Town, where an LAI PrEP trial is getting underway), vaccine trials and, someday, passive immunization (right now these antibodies can only be administered via a three-hour transfusion, as we learned at an incredibly accessible presentation by self-described “lab rat’ Penny Moore).

It was clear from this “after hours” discussion that, whilst the focus of community involvement primarily by researchers is within trial communities, there is a need for basic concepts of research and processes to be understood by these broader groups. Addressing this as a gap can go a long way into creating an even more supportive environment for trials and research. Since when civil society understands core concepts and questions related to biomedical research, they are more likely to engage, inform and participate. This would further ensure a natural progression of successful science to real life public health policy and implementation. Whilst globally, initiatives by organizations like AVAC seek to address this, strong and sustained partnerships between science and civil society with countries remain a lingering question as to how this should happen and whose responsibility it is.

I developed a slide set that summarized the pipeline we grappled with and some of the key findings and suggestions that came out of this meeting. There were more questions than answers, as you’ll see. If you want to learn more, raise new questions—or get involved in providing some answers—please be in touch!

Prevention on the Line Webinar Series

AVAC is putting together a year-long series of web-based dialogues focused on HIV prevention research and implementation. This series, HIV Prevention on the Line, will delve into issues raised in our recent AVAC Report and engage with issues and priorities that emerge over the course of the year.

Slides, audio and animations from the first set of webinars are available below. Stay tuned to this page, or subscribe to our Advocates Network newsletter, for details on future webinars.

Vaccines in Vivo: Advances in AIDS Vaccine Research
This year brought the launch of long-awaited initiation of clinical trials building on positive results from the RV144 “Thai” trial. This effort is led by the Pox-Protein Public-Private Partnership (P5), including the the HIV Vaccine Trials Network, who joined the webinar to provide a status update of their current vaccine research and development program. We also featured Janssen, part of Johnson & Johnson, to provide an overview of the research program they are moving forward that focuses on a cross-clade vaccine product.

May 18, 2015 — Downloads: Slides (PDF) / Audio (MP3) / Animation (Flash)

New Frontiers in HIV Prevention, Treatment and Cure: An advocate’s webinar on passive immunization
This webinar focused on “passive immunization”—a scientific term for an expanding area of research that’s highly relevant to treatment, prevention and cure work. There are trials in humans happening in many regions of the world—and data are beginning to come in that advocates need to understand, analyze and consider.

This hour-long webinar featured Dr. Sarah Schlesinger (Rockefeller University) who provided an overview of recent developments across the field including new data from Rockefeller.

April 21, 2015 — Downloads: Slides (PDF) / Audio (MP3) / Animation (Flash)

Demanding Clarity on PrEP: Understanding recent data on oral PrEP

This webinar featured Jean-Michel Molina of the French research agency ANRS and Sheena McCormack of the UK Medical Research Council discussing the data from the IPERGAY and PROUD studies, respectively. Both trials evaluated oral TDF/FTC (brand name Truvada) as PrEP in gay men and other men who have sex with men, and both reported high levels of protection against HIV acquisition. PROUD prescribed a daily pill regimen; IPERGAY asked trial participants to follow an “event driven” regimen that involved a sequence of doses before and after sex. IPERGAY participants took an average of four doses per week—comparable to the estimated protective dose required in trials of daily oral PrEP.

March 12, 2015 — Downloads: Slides (PDF) / Audio (MP3) / Animation (Flash)

Follow the Money: Knowns and unknowns when it comes to cash transfers and financial incentives to improve health in people living with and/or at risk of HIV
This webinar featured Wafaa El-Sadr, principal investigator of HPTN 065, which evaluated the use of cash incentives in improving outcomes for people living with HIV in the United States.

March 11, 2015 — Downloads: Slides (PDF) / Audio (MP3) / Animation (Flash)

After FACTS: What’s next for HIV prevention in women?
Helen Rees, principal investigator of the FACTS 001 microbicide trial of vaginal 1% tenofovir gel, spoke of their findings of no evidence of protection overall associated with the vaginal gel. Jared Baeten, co-chair of Partners PrEP, discussed the Partners Demonstration Project finding that serodiscordant couples using oral PrEP and/or ART had ver low levels of HIV transmission. We discussed what these and other data meant for women, including young and adolescent girls.

March 9, 2015 — Downloads: Slides (PDF) / Audio (MP3)

Does Sex Have Impact on HIV Prevention Research?

This post was written by Morenike Folayan, Coordinator of the New HIV Vaccine and Microbicide Advocacy Society and member of the CROI Community Liaison Subcommittee.

At the CROI meeting, I seem to be getting signals that sex significantly impacts HIV research design, data interpretation and data use.

First, I learned that availability of tenofovir, the drug used for pre-exposure prophylaxis (PrEP), is 10 to 100 times lower in the vagina tissues than the rectal tissues when taken orally. This therefore implies that the results of PrEP studies conducted to assess HIV transmission through anal sex cannot be automatically translated to imply the results would be pan out the same way when considering vaginal sex. Hmmmm.

Second, I also learned, through informal conversation with those who work in the field for ARV studies, that the reasons many HIV positive men decide to commence ARV use for HIV prevention (treatment as prevention, or TasP) differ from the reasons why women do commence TasP. More men commence TasP out of a sense of protection of their sexual partner—they have a higher sense of responsibility to protect their sexual partner from getting infected. Women on the other hand, commence the use of TasP simply because they are eligible to use the product. I found that very interesting. I think there may be cultural differences in this observation. I doubt if this is the case in Africa. However, like the lessons we learn from CROI, we need evidence. I would like to see a formal study evaluate this social context of TasP use by men and women in different cultural setting.

Third, the iPrEx OLE study showed increase uptake of, and adherence to, PrEP by MSM who were at high risk for HIV infection. In the VOICE study, we see less uptake and adherence by women who were at high risk of HIV infection. Hmmm. Are we starting to see differences in cultural perception of risk or is this truly a sex difference in risk perception?

(Editor’s note: In iPrEx OLE, participants knew that they were being offered an effective prevention tool—it was an open label study; in VOICE, women were counseled that they might be receiving a placebo and that none of the strategies were proven. Understanding how context—research site, clinic, public health program or community center—affects uptake and risk perception is also key.)

Reason for more studies on sex differences in PrEP and TasP use. Maybe conducting studies with transgenders may help address this question. Maybe.

CROI Through a Pharmacist’s Perspective

William Larson is an HIV medication adherence pharmacist working in Minneapolis, MN as part of the Ryan White program. He strives to increase HIV treatment literacy in disproportionately impacted communities. He is a graduate of the Black AIDS Institute’s Community Mobilization College in 2013.

Last week I attended CROI 2015 as a community educator scholarship recipient from CROI, in association with the Black AIDS institute and AVAC. It has been a rare opportunity to hear first-hand live presentations of new research by leading HIV researchers.

I got to meet several of the researchers at breakfast updates for scholarship recipients. What an opportunity! I was impressed by the researchers’ approachability and willingness to answer questions.

I was also impressed by the committed and knowledgeable scholarship recipients, all of whom are eager to better understand the new research so that they could bring the information back to their home communities.

As a pharmacist working in HIV medication adherence, I am interested in new therapeutic agents for the treatment of HIV. Information was presented on a new compound, tenofovir alafenamide or TAF as part of single tablet regimen also containing elvitegravir, cobicistat and emtricitabine. This was compared to the currently available single tablet medication, Stribild, which contains elvitegravir, cobicistat, emtricitabine and tenofovir disaproxil fumarate (TDF).

TDF (Viread) is a frequently used medication and part of most HIV treatment regimens. It is found in the combination product Truvada and the single tablet regimens Atripla, Complera and Stribild. Although considered safe for most patients, there are concerns about bone and kidney changes which can occur in some patients with long-term use.

In research presented by Dr. David Wohl, TAF was found “non-inferior” to TDF in achieving viral suppression irrespective of age, sex, race, viral load or CD4 count. In simpler terms, TAF is at least as effective as TDF. Both drugs had low rates of viral resistance and both were well tolerated.

Dr. Paul Sax presented data on renal and bone safety of TAF compared to TDF. This research demonstrated that TAF has less effect on the kidney (serum creatinine and urinary protein) and bone (bone mineral density) compared to TDF, with slightly higher lipid levels from TAF.

In the clinic where I work, we are discontinuing or replacing TDF weekly in select patients with elevated creatinine levels. Although we are discontinuing TDF less often for bone changes, it is possible that is a problem which might be detected or develop later in patients on life-long therapy.

Why does TAF appear to be safer than TDF, with fewer kidney and bone changes? Compared to TDF 300 mg, TAF 25 mg produces 90 percent lower level of tenofovir in the plasma. Tenofovir is responsible for the bone and kidney changes. TAF, like tenofovir, is converted to tenofovir diphosphate intracellularly and this is the compound with antiviral properties.

Tenofovir alafenaide or TAF is a safer and equally effective alternative to TDF, and will likely become the preferred alternative for individuals now receiving a TDF-containing product.

My sincere thanks to CROI, AVAC and the Black AIDS Institute for allowing me and others to attend CROI and their commitment to disseminating the latest research to our most heavily-impacted communities in the United States and around the globe.

A Target That Worked: 3 by 5

Appearing in AVAC Report 2014/2015: HIV Prevention on the Line, this graphic shows how a target was set and met to provide ART Treatment U=U to 3 million people.

Global ART Coverage (2014)

This graphic, which appears in the AVAC Report 2014/15: HIV Prevention on the Line, depicts global ART coverage.

AVAC Report: HIV Prevention on the Line

AVAC’s annual report of the field, the upcoming CROI meeting and why the coming year is the best and worst of times for HIV prevention

Next week, scientists, advocates and clinicians will gather in Seattle for the Conference on Retroviruses and Opportunistic Infections (CROI), a venerable HIV meeting that often triggers media coverage of the AIDS epidemic and the potential for curbing it and preserving health in people living with HIV.

A range of data is expected from CROI including “late-breaker” abstracts that will showcase data from IPERGAY and PROUD, two trials of oral PrEP using TDF/FTC in gay men and other men who have sex with men in Europe and Canada, and another trial of the microbicide 1% vaginal tenofovir gel in South African women. There will also be data from a PrEP “demonstration project” that provided the strategy in a real-life context for Kenyan and Ugandan couples with one HIV-positive and one HIV-negative partner.
We don’t know what the specific headlines will be, but we can say with confidence that one take-away must be this: The future of HIV prevention is on the line.

In our latest report, AVAC Report 2014/15: Prevention on the Line, we provide a clear agenda for what needs to happen, what’s missing, and why it matters now more than ever before.

Specifically, we argue that:

  • Ambitious prevention goals matter. They can galvanize new action, in part by expanding our sense of what’s possible.
  • But these goals will only work if they’re feasible, well-defined, measurable, and backed by adequate resources and political support. The prevention goals issued so far are inspiring but they don’t yet meet those requirements.
  • As the UNAIDS “Fast Track” for 2020 set aspirational goals, clear short-term targets are also urgently needed. We can’t wait for five years to see if the world is on track to end the AIDS epidemic.
  • The global AIDS response is running at a major financial deficit. New targets will not be met—and may even be irrelevant—if we fail to close a growing global funding gap.

Recent breakthroughs in HIV research have transformed the ability to curb new infections, making it possible to contemplate the end of the global AIDS epidemic. But prevention could be left behind if global leadership fails to make it a priority.

Recently, UNAIDS issued broad goals for HIV testing, ART provision and virologic suppression over the next five years. According to the agency, achieving these “90-90-90” goals would put the world on track to effectively end the AIDS epidemic by 2030.

On the prevention front, UNAIDS seeks to reduce new infections worldwide from 2.1 million in 2013 to 500,000 in 2020, and to eliminate stigma and discrimination. These are ambitious goals and worth aspiring to. But something important is missing from the picture—intervention-specific targets with the specificity, strategy and resources to match. The goal is great. What’s missing is how to get there.

In twenty years, we will have ample hindsight as to whether today’s targets mattered in the quest to end AIDS.

But right now, foresight and focus are urgently required. We’re concerned about whether the targets that have been set are the right ones, how much targets matter—particularly in the context of a global response running at a disastrous funding deficit—and where prevention targets other than those focused on the antiretrovirals in HIV-positive individuals—fit in. We’re also cognizant that targets can turn from audacious to absurd in the blink of an eye if financing, political will and community buy-in are missing.

AVAC works in coalitions in many of the countries hardest hit by the epidemic. Targets that are developed Geneva, Washington DC and other corridors of power can bear little resemblance to the realities of AIDS endemic countries and communities. Where there’s no reality, there’s no relevance. It’s essential that countries have the technical and financial resources to make global targets relevant to national context. Otherwise, the loftiest goals will be ignored.

As we argue in this Report, targets have played a critical role in changing the course of the epidemic. Likewise, a poorly-thought out target can have no impact at all. Right now, it’s critical that targets and tactics are matched to the lofty but achievable goal of bringing an end to AIDS. This is why we’ve devoted the first section of the Report to a look at why targets matter, what targets are missing, and how advocates for a comprehensive response need to work together to ensure smart, strategic targets across the spectrum of prevention options.

We also focus on issues that underpin (and, sometimes, undermine) the ability to meet these targets. We identify three specific areas for action:

  • Align high impact strategies with human rights and realities. Biomedical advances of the past eight years have made it scientifically plausible to talk about ending the epidemic. But plausible doesn’t mean possible. Today some scientists and public health professionals are focused on what can be achieved biomedically—without enough attention to the structural and social contexts in which treatment prevention are delivered. At the same time, some rights-focused partners speak of HIV as being exclusively pill-oriented, suggesting that there isn’t any dynamism or action on the rights-based fronts. It need not be a permanent rift—indeed it cannot be. If science does not get synched up with human rights then then there is little hope of bringing the epidemic to a conclusive end.
  • Invest in an oral PrEP-driven paradigm shift. The world is failing to deliver the most effective interventions with smart strategy and at scale. Daily oral PrEP for HIV prevention is just one example. Global targets for PrEP may be released in the coming months, but there aren’t any plans in place to meet them. Demonstration projects are small and disconnected, funding is limited and policy makers aren’t heeding the growing demand from men and women, including young women in Africa. Now is the time to spend and act to fill these gaps.
  • Demand short-term results on the path to long-term goals. It will be years before the world has an AIDS vaccine, cure strategies, long-acting injectable ARVs or multipurpose prevention technologies that reduce the risk of HIV acquisition and provide contraception. But there’s plenty of activity in clinical trials and basic science for these long-term goals. This activity needs to be aligned with short-term goals that can be used to measure progress and manage expectations.

As AVAC Report goes to press this week and as we prepare for CROI next week, the United States is grappling with profound questions about the ways that the lives of Black men and women are valued under the law. The world is trying to understand how the West African Ebola epidemics got out of control—and how to bring them to an end. And there is continued concern and vigilance over anti-homosexuality laws in Nigeria and the Gambia, and in hate-mongering environments and legislation that endanger LGBT individuals and many other marginalized groups around the world.

These events are not separate from the work that we do to fight AIDS. They embody the issues of racism, inequity, poverty and security that drive the epidemic that must be addressed to end it. In addition to the HIV-specific work laid out in these pages, it is essential to work towards fundamental, lasting and positive change in each of these areas. That will be history-making, indeed.

Press Release

With future of HIV prevention “on the line,” AVAC calls for sharper, bolder strategy to end the epidemic

Contacts

Mitchell Warren, mitchell@avac.org, +1-914-661-1536

Kay Marshall, kay@avac.org, +1-347-249-6375

New York — In a report issued today, AVAC warned that global HIV prevention efforts are in jeopardy due to an absence of strategic targets, resources and specific implementation plans to translate science, slogans and goals into action. The report calls for a robust set of global HIV prevention targets tailored to specific interventions and demands action in several key areas of the global AIDS response, including expanded rollout of daily oral pre-exposure prophylaxis, or PrEP, and alignment of science and human rights-based agendas.

“We’re at a make-or-break moment and the future of HIV prevention is on the line,” said Mitchell Warren, AVAC’s executive director. “Advances in HIV treatment and prevention research have made it possible to contemplate ending the AIDS epidemic in our lifetimes, but that will only happen with smarter planning, increased resources and greater accountability.”

The report was released ahead of the Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle (Feb. 23-26), where researchers are expected to present data from several major HIV prevention trials, including studies that could help drive global implementation of PrEP, as well as a key study of a tenofovir-based vaginal gel for women.

Report calls for smart, realistic goals and targets for HIV prevention

Today’s report, entitled Prevention on the Line, takes a close look at global goals for HIV prevention and what it will take to make them a reality. UNAIDS recently adopted the broad goals of reducing new HIV infections worldwide from 2.1 million in 2013 to 500,000 and eliminating stigma and discrimination, both by the year 2020.

Drawing upon lessons from WHO’s “3 x 5” HIV treatment initiative and other case studies, the AVAC Report concludes that ambitious prevention goals are critical – but that they will only work if they’re feasible, well-defined, measurable and supported with adequate resources and political commitment. In the case of the new UNAIDS prevention goals, the report points to a critical need for more specific, interim targets that can be tracked between now and 2020; for better data and monitoring approaches; and for resource allocations that are directly tied to achieving those targets.

“The UNAIDS prevention goals for 2020 are ambitious and inspiring,” said Warren. “But something important is missing from this picture: how to get there. We need a clear path forward, including short-term targets, so we don’t wait five years to see if the world is on track. And new targets won’t be met – and may even be irrelevant – if we fail to close the growing global funding gap for HIV prevention.”

Bold action needed to advance AVAC’s agenda to end AIDS

The report also recommends key actions to advance AVAC’s three-part agenda to end AIDS. First issued in 2011, the agenda calls for sustained efforts to deliver proven prevention tools, demonstrate and roll out new options such as PrEP and develop long-term solutions such as long-acting ARV-based prevention, vaccines and cure strategies.

Key recommendations for 2015 include:

1. Align high-impact HIV prevention with human rights and realities. Research has demonstrated the potential of high-impact prevention strategies, including biomedical approaches like HIV treatment for people living with HIV and voluntary medical male circumcision (VMMC). But these strategies won’t succeed in the real world if we give short shrift to human rights concerns, or if we fail to involve affected communities in designing and implementing prevention programs. Recent experience with treatment and VMMC, in particular, has shown that community buy-in is an essential ingredient of successful rollout and scale-up.

2. Invest now to scale up access to PrEP. Landmark trials have shown that daily oral PrEP is a powerful HIV prevention tool, and studies at next week’s CROI meeting could provide additional support. But the pace of rollout remains far too slow. Demonstration projects are small and disconnected, funding is limited and policy makers are not yet heeding growing demands for access. Funders should invest now in large-scale targeted implementation of PrEP, linked to national programs. National regulatory authorities and health ministries should prioritize licensure and rollout.

3. Accelerate research into long-term solutions. We must sustain and accelerate research on solutions such as an effective AIDS vaccine, long-acting antiretroviral prevention and treatment and a cure. Just like the rest of the AIDS response, this research needs its own short-term targets, aligned to long-term goals.

The new report and related resources, including downloadable graphics, are available now at www.avac.org/report2014-15.

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About AVAC: Founded in 1995, AVAC is a non-profit organization that uses education, policy analysis, advocacy and a network of global collaborations to accelerate the ethical development and global delivery of AIDS vaccines, male circumcision, microbicides, PrEP and other emerging HIV prevention options as part of a comprehensive response to the pandemic.